Pharmaceutical Inorganic Chemistry

By V. Alagarsamy

Pharmaceutical Inorganic Chemistry is a much awaited great work in the Pharmacy. Targeted mainly to B. Pharmacy & Pharm-D students, this book will also be useful for B.Sc. as well as M.Sc. chemistry and pharmaceutical chemistry students. The main object of this book is to attract the under graduate and post graduate students, to learn the basic theories of Pharmaceutical Inorganic Chemistry. Thus the book is aimed to eliminate the inadequacy in teaching and learning of Pharmaceutical Inorganic Chemistry by providing enormous information about the inorganic compounds used in Pharmacy.
·         The content of the book is innovative and presented in eight chapters, in a concise form as per the needs of the students.
·         Incorporation of all the Chemical & Pharmaceutical aspects of the inorganic compounds and their formulations.
·         Describing all the aspects of inorganic pharmaceuticals in easy to understand manner is the first of its kind.
·         For each chapter, a brief introduction, detailed discussion of the basic theory and applications in pharmacy are provided.
·         Pharmaceutically important inorganic pharmaceuticals are discussed in detail with the sources, official standards, preparations, physical and chemical properties, tests for identification, uses and their storage conditions.
·         The principles of assay of each compound, which is difficult to remember by the students is described in a student friendly manner to understand easily and able to reproduce well in examinations, is the first of its kind.
·         Presentation with simplified way of explanation along with chemical reactions of all compounds  helps to reproduce well in examinations. 
The coverage is complete when compared to the all University syllabus in India, AICTE and the PCI syllabi.
Contents:
1. Introduction to Pharmaceutical Inorganic Chemistry 
2. Basics of pharmaceutical Inorganic Chemistry
3. Acids, Bases and Buffers 
4.Quantitative Analysis (Volumetric and Gravimetric Analysis) 
5. Quality Control and test for Purity 
6. Inorganic Pharmaceuticals (Inorganic Compounds used in Pharmacy) 7. Radiopharmaceuticals 
8. Coordination Compounds
About the Author: 
V. Alagarsamy, M. Pharm., Ph.D. FIC, DOMH, is Professor and Principal of MNR College of Pharmacy, Sangareddy, Gr. Hyderabad. He received his D. Pharm from Coimbatore Medical College, B. Pharm degree from Madurai Medical College, M. Pharm from LM College of Pharmacy, Ahmedabad, Ph.D., from The MS University of Baroda. He has been teaching Pharmaceutical Inorganic Chemistry, Chemistry of Natural Products & Medicinal Chemistry and performing research work in synthetic medicinal chemistry on novel heterocyclic bio-active compounds for more than a decade. For his research work, he has collaborated with various research laboratories/organizations like National Cancer Institute, USA; Rega Institute for Medical Research, Belgium; Southern Research Institute, USA; and Sudbury Regional Hospital, Ontario, Canada. He is a recipient of Young Scientist award from the Department of Science and Technology, New Delhi. 

• Language: English
• Publisher: BSP BOOKS
• Release date: Oct 22, 2019
• ISBN: 9789386211880

Book preview

CHAPTER 1

INTRODUCTION TO PHARMACEUTICAL INORGANIC CHEMISTRY

1.1 PHARMACEUTICAL CHEMISTRY

Pharmaceutical Chemistry is a branch of chemistry that deals with the chemical, biochemical and pharmacological aspects of drugs. It includes synthesis/isolation, identification, structural elucidation, structural modification, Structural Activity Relationship (SAR) studies, study of the chemical characteristics, biochemical changes after drug administration and their pharmacological effects.

1.1.1 Inorganic Chemistry

Inorganic chemistry is the study of all the elements and their compounds except carbon and its compounds (which is studied under organic chemistry). Inorganic chemistry describes the characteristics of substances such as nonliving matter and minerals which are found in the earth except the class of organic compounds. Branches of inorganic chemistry include coordination chemistry, bioinorganic chemistry, organometallic compounds and synthetic inorganic chemistry. The distinction between the organic and inorganic are not absolute, and there is much overlap, especially in the organometallic chemistry, which has applications in every aspect of the pharmacy, chemical industry–including catalysis in drug synthesis, pigments, surfactants and agriculture. In short, Inorganic chemistry is the branch of chemistry that deals with inorganic compounds. In other words, it is the chemistry of compounds that do not contain hydrocarbon radicals.

1.1.2 Inorganic Compounds

These are traditionally viewed as compounds being synthesized by the geological systems and lack hydrocarbon (carbon-hydrogen). In contrast, organic compounds are those found in biological systems. In general organic chemists say any molecule containing carbon as an organic compound and hence this means that inorganic chemistry deals with the compounds or molecules which lack carbon atom. Berzelius, the 19th century chemist, described inorganic compounds as inanimate. The first important synthetic inorganic compound was ammonium nitrate for soil fertilization. Inorganic compounds are found in nature as minerals. Soil contain iron sulfide as pyrite or calcium sulfate as gypsum. They are also found multitasking as biomolecules: As electrolytes (sodium chloride), in energy storage (ATP) or in construction (the polyphosphate backbone in DNA). Inorganic compounds are synthesized for use as drugs such as cisplatin, magnesium hydroxide, catalysts such as vanadium (V) oxide and titanium (III) chloride, or as reagents in organic chemistry such as lithium aluminium hydride.

Medicinally useful substances are derived from either organic or inorganic sources. Naturally obtained compounds attracted the attention of humans always, in which inorganic chemicals contributing significantly in some of the ailments, even after the development of many drugs from synthetic and plant sources. Many of the inorganic salts (antimony, arsenic and mercury) are known to be poison, still they are used in medicine cautiously. Some of them are replaced by the organic medicines.

Study of pharmaceutical applications of the inorganic compounds led to the establishment of a new avenue called Pharmaceutical inorganic chemistry, which deals

with the study of both non-essential and essential elements about their preparation, standards of purity, test for identification, limit tests to be performed for determining the quality and extent of purity, storage, different formulations and their storage conditions and therapeutic uses.

The term ‘Pharmaceutical’ is used for any chemical substance useful in preventive or therapeutic or which finds use in the preparation of medicament. Some find use only in the laboratory during the preparation but may not be present in the final product, these are also incorporated under pharmaceuticals. Quality of all these pharmaceuticals must be carefully controlled. For this reason specifications of quality are mentioned for each pharmaceutical. These descriptions are reported in the pharmacopoeia.

1.1.3 Importance of Inorganic Pharmaceuticals

Inorganic pharmaceuticals are useful in any of the following ways.

1.   Useful medicinally for their therapeutic purpose. Example: Astringents and antimicrobials etc.

2.   Useful as pharmaceutical aids. Example: Bentonite, talc etc.

3.   To change the reaction of body fluid. To acidify or alkalise. Example: Antacids, alkalis, mineral acids.

4.   Replacing or replenishing the normal content of body fluids. Example: Sodium, potassium, calcium, chloride, phosphate etc.

5.   Useful as reagents to carry out the reactions. Example: Catalysts (platinum, nickel) oxidizing and reducing agents (lithium aluminium hydride).

6.   Useful in Pharmaceutical analysis. Example: Titrants such as potassium permanganate etc.

Various uses of inorganic pharmaceuticals in pharmacy are presented herein

Abrasives: Drugs which are used for the cleaning and whitening of teeth. Example: Dibasic calcium phosphate.

Absorbents: Drugs which are used to absorb the toxins and bacteria in the GIT. Example: Calcium carbonate.

Acidifiers: Drugs which are used to enhance the acidity temporarily in GIT. Example: Dilute hydrochloric acid.

Adsorbents: Drugs which are used in the treatment of mild dysentery or diarrhoea or other disturbances of GIT due to their ability to adsorb gases, toxins, and bacteria. Example: Bismuth subcarbonate, Bismuth subnitrate.

Alkalizers: Drugs which are used to induce the alkaline condition or used in acidic condition of body. Example: Sodium citrate.

Anaesthetics: Drugs which are used to produce reversible loss of sensation. Example: Nitrous oxide.

Analgesic: Drugs which are used to relieve pain. Example: Nitrous oxide.

Antacids: These are drugs which are usually alkaline substances, used for neutralizing excess acid in the stomach. Example: Aluminium hydroxide gel, Calcium carbonate, Magnesium carbonate.

Anthelmintics: Compounds used for the treatment of worm infestations or schistosomiasis. Example: Ammoniated mercury, Sodium antimony tartarate.

Antibacterial: Drugs which are used in the treatment of bacterial infections. Example: Yellow mercuric oxide (ophthalmic).

Anticonvulsants: Drugs which are used for the treatment of epilepsy. Example: Potassium bromide.

Anti coagulants: Drugs which are used to prevent blood clotting. Example: Sodium citrate.

Anti depressants: Drugs which are used in the treatment of depression. Example: Lithium carbonate.

Antidotes: Drugs which are used in the treatment of poison. Example: Sodium nitrite, Sodium thiosulphate.

Antifebriles: Drugs which are used to relieve pain or reduce fever. Example: Ammonium acetate.

Antifungal agents: Drugs which are used in the treatment of fungal infections. Example: Zinc undecylenate (topical use), Potassium iodide.

Antihypercalcemic agents: Drugs which are used in the treatment of abnormal calcium concentration in the body. Example: Sodium acid phosphate.

Anti infectives: Drugs which are used in the treatment of local infections. Example: Potassium permanganate, Silver nitrate, Hydrogen peroxide, Boric acid.

Anti inflammatory agents: Drugs which are used in the treatment of inflammatory pain (Rheumatoid arthritis). Example: Sodium aurothiomalate.

Anti irritant agents: Drugs which are used to prevent irritation or allergic reactions. Example: Aluminium metal powder.

Antiseptics: Drugs which are used to inhibit the growth and development of micro organism without killing. Example: Strong iodine solution.

Antiperspirants: Drugs which are used to remove the bad odour in body. Example: Aluminium sulphate.

Anti-protozoals: Drugs which are used in the treatment of protozoal infections or Leishmaniasis. Example: Sodium antimony gluconate.

Anti pruritics (topical): Drugs which are used in the production of soothing effect in the skin. Example: Calamine.

Anti rheumatics: Drugs which are used in the treatment of rheumatism. Example: Sodium aurothiomalate.

Anti thyroids: Drugs which are used in the treatment of thyrotoxicosis. Example: Potassium perchlorate.

Anti tumor agents: Drugs which are used in the treatment of cancer. Example: Cisplatin (Testicular and ovarian cancer).

Anti schistosomal agents: Drugs which are used in the treatment of schistosomiasis. Example: Sodium antimony tartrate.

Antioxidants: Substances that prevents or delays oxidation. Some formulations, vegetable oils and prepared foods contain antioxidants. Example: Sodium bisulphate, sodium metabisulphite, sodium sulphite.

Astringents: These are the substances which bring about protein precipitation. Astringent action is evidenced by contraction and wrinkling of tissue and by blanching. Example: Calamine, Aluminium citrate.

Bactericides: Drugs which are used to kill bacteria. Example: Potassium permanganate.

Bacteriostatics: Drugs which are used to prevent the growth of bacteria. Example: Alum, borax (local bacteriostatic).

Bleaching agents: Drugs which are used in the cleansing of wounds or bleaching. Example: Hydrogen peroxide.

Buffers: Substance which prevents the change in pH upon addition of acid or base. Example: Acetate buffer (pH – 3.9), Sodium citrate buffer.

Calcium supplements: Drugs which are used as a calcium source. Example: Calcium lactate, Calcium gluconate.

Cathartics: Drugs which are used to enhance defecation, removes constipation and expulsion of intestinal parasites. Example: Calomel, Magnesium sulphate.

Chlorine source: Substance which liberates chlorine. Example: Chlorinated lime, Chlorinated soda.

Dentifrices: Drugs which are used in cleaning the surface of the teeth. Example: Calcium carbonate, Magnesium peroxide.

Depilatory agents: Drugs which are used to remove hair. Example: Barium sulphide.

Diagnostic agents: Drugs which are used in diagnose the diseased conditions of the organs. Example: Barium sulphate.

Diaphoretics: Drugs which are used to promote sweating. Example: Potassium citrate.

Disinfectants: Drugs which are used to kill the microbes in nonliving things. Example: Ammonium acetate.

Diuretics: Drugs which are used to increase the urine output. Example: Ammonium chloride, Ammonium iodide.

Dressing material: Substances which are used for the dressing of burns. Example: Aluminum metal foil.

Dusting powders: Substance which are used to have soothing effect on the skin. Example: Talc, Zinc stearate, Light kaolin.

Electrolyte replenishers: Compounds used to treat acid base imbalance conditions in the body. Example: Sodium chloride, Ringer lactate solution, Potassium chloride.

Emetics: Drugs which are used to induce vomiting. Example: Zinc sulphate, Copper sulphate.

Expectorants: Drugs which are used in the treatment of cough. They promotes the ejection of mucus (sputum) from the lungs, bronchi and trachea by increasing its fluidity (reducing viscosity). Example: Potassium iodide (sedative expectorant), Eucalyptus, Lemon (stimulant expectorant), Ammonium chloride, Potassium iodide.

Fillers: Drugs which are used to fill the dental cavities. Example: Gold and Silver metals.

General anaesthetics: Drugs which are used to produce reversible loss of sensation. Example: Nitrous oxide.

Germicides: Drugs which are used to kill the germs. Example: Chlorinated lime.

Haematinics: Drugs which are used in the treatment of anaemia. Example: Ferrous sulphate, Ferric ammonium citrate and other iron compounds.

Haemostatic: Drugs which are used to arrest the flow of blood. Example: Alum.

Inhalants: Inhalants are the drugs or chemicals which in the vapour form are inhaled or administered through the respiratory system in the body. Example: Oxygen, CO2, Ammonium carbonate, Nitrous oxide, Helium.

Iodine supplements: Drugs which are used in the treatment of iodine deficiency. Example: Potassium iodide.

Laxatives: Drugs which are used to promote the evacuation of bowel. Example: Magnesium Sulphate, Sodium phosphate.

Protectives: Substance which tend to form a coating and protect the exposed skin or mucus membrane from harmful stimuli. Example: Zinc stearate, Zinc oxide.

Purgatives: Drugs which are used to defecate. These agents relieve constipation and helps in the expulsion of intestinal parasites. Example: Magnesium sulphate.

Radiation shields: Compounds which are used to prevent the entry of radiations. Example: Lead sheets, Wall lining.

Radio isotope tracers: Radioactive element or compound added to material to monitor the material’s distribution as it progresses through a system. Example: Carbon-14, Tritium.

Radiotherapeutic agents: Radioisotopes used for the treatment of diseases. Example: Iodine-121, Cr- 52 and Gold- 198.

Rubifacients: Substances which causes reddening of skin by dilating blood vessels and increasing blood circulation in the applied area. Example: Ammonia.

Scabicides: Drugs which are used in the treatment of scabies. Example: Sulphur.

Sedatives: Substance which causes CNS depression and produces sedation. At higher dose they produce sleep. Example: Potassium bromide, Lithium carbonate.

1.2 PHARMACOPOEIA

The word Pharmacopoeia is derived from Greek words ‘pharmakon’ means a drug (both remedy and poison) and ‘poiein’ means to make or create. Pharmacopoeia is a book containing directions for the identification of samples and the preparation of compound medicines, and published by the authority of a government or a medical or pharmaceutical society. For this reason Pharmacopoeia is a legislation of a nation which sets standards and mandatory quality indices for drugs, raw materials used to prepare them and various pharmaceutical preparations.

1.2.1 Monograph

In simple way monographs are descriptions of pharmaceutical preparations. In broader way it is a reference work for pharmaceutical drug specifications. It is a complete description of a specific pharmaceutical, which includes chemical formulae, atomic and molecular weight, definition, statement of content, category, dose, usual strength, description, solubility, identification tests, assay, other test, limits of impurities, quantities, and conditions for storage. The appendices include standards for apparatus, reagents and solutions, indicators, reference substances, test animals, calculation of results, other chemicals techniques, processes etc. of the concerned pharmaceuticals.

By the direction of the council of the pharmaceutical society of the certain nations, the world’s most comprehensive source of drug information in a single volume is published periodically in the society’s department of pharmaceutical sciences.

It is the traditional activity, to help the practicing pharmacists and physicians aiming to provide unbiased concise reports on the actions and uses of most of the world’s drugs and medicines. By reflecting clinical practice, every publication of Pharmacopoeia monographs are accurately organized based on the updated needs of today’s pharmacist. In the form of new monographs the details are provided for new compounds and some of the previous monographs which are not in continued use are deleted. The overall effect is to provide an increase in the average of drugs with typographically improvements to assist the reader in locating sections of a monograph.

With the search for an effective treatment of diseases a few of the developing therapeutics are revised continuously in Pharmacopoeia. Example: Anti HIV agents. In Pharmacopoeia the drug’s distinguished features are updated, renewed and discussed for the treatment of infections and development of antiviral, antiprotozoal and antibacterial therapy. Along with novel approaches in the treatment advances in the cardiovascular group of drugs are included. The other areas like anti-malarial drugs, anti-neoplastic agents, anti-parkinsonism drugs etc. are also included in Pharmacopoeia.

Based on the published information, Pharmacopoeia is divided in to three different major parts. Each part is comprised of several chapters.

Part I: Generally the drugs that have similar use or actions are bringing together by part I of Pharmacopoeia. In related chapters to guide reader the cross references is used to find out the drug that may be of interest. The common actions of the groups of drugs are provided as background information in many of the chapters.

Part II: Monographs of new drugs, drugs under investigation, drugs which are not easily classified and obsolescent drugs still of interest are presented in part II of Pharmacopoeia. It also provides details regarding effects of required drug therapy.

Part III: Composition of the proprietary medicines that are advertised to the public in different countries are documented with omission of herbal medicine in part III of Pharmacopoeia.

Only the pharmaceuticals which are commonly and currently in use are included in the Pharmacopoeia; whereas the substances which are found to be undesirable and are not currently in use are excluded. Moreover part of Pharmacopoeia may also comprise the pharmaceuticals which are used for application or internal consumption by human beings.

In the Pharmacopoeia only minimum standards are prescribed for pharmaceuticals, but with more stringent standards the manufacturer may supply these substances. Hence a drug has to obey strictly the standards prescribed by any one of the Pharmacopoeias. The medication may be considered as substandard if it does not obey these standards and usually it is not prescribed by medical practitioners.

1.2.2 History of Pharmacopoeia

Each country has legislation on pharmaceutical preparations which sets a standards and required quality indices for medicament, raw materials and preparations employed in the manufacture of drugs. These regulations are presented in separate articles. General and specific matters relating to individual drugs are published in the form of a book called a Pharmacopoeia.

On 15th December 1820, the first United State Pharmacopoeia (U.S.P) was released. In 1864, the first British Pharmacopoeia (B.P) was published with inclusion of monographs on benzoic acid, gallic acid, tartaric acid, tannic acid, camphor, lactose, sucrose and seven alkaloids along with their salts.

1.3 INDIAN PHARMACOPOEIA

British Pharmacopoeia was utilized as the official book of standards in India before independence. The actual process of publishing the first Indian Pharmacopoeia started in the year 1944 under the chairmanship of Col. R. N. Chopra. The Indian Pharmacopoeia list was first published in the year 1946 and was put forth for approval. The government of India constituted a permanent Indian Pharmacopoeia Committee in 1948 for the preparation of the Indian Pharmacopoeia and established a central Indian Pharmacopoeia Laboratory at Ghaziabad, Uttar Pradesh to keep it up to date. The Indian Pharmacopoeia is published in fulfillment of the requirements of the Drugs and Cosmetics act, 1940 and rules there under.

The drugs and cosmetics act 1940 stated that the Indian Pharmacopoeia is the book of standards for drugs included therein and the standards as included in the Indian Pharmacopoeia would be official. If considered necessary, these standards can be amended and the secretary of the Indian Pharmacopoeia committee is authorized to issue such amendments.

Government of India, Ministry of Health and Family welfare publishes Indian Pharmacopoeia based on the recommendation of Indian Pharmacopoeia committee (in accordance with Drugs and Cosmetics Acts 1940, Dangerous Drugs Act 1930, and Poisons Act 1919 and the rules framed there under). In general, the general notices and appendices included in the Indian Pharmacopoeia and as amended in addendum apply both to the matter contained in the Indian Pharmacopoeia and to the matter contained in this Addendum.

After independence, the first edition of the Indian Pharmacopoeia (I.P) was published in the year 1955 under the chairmanship of Dr. B. N. Ghosh. Supplement for first edition of Indian Pharmacopoeia was published in the year 1960. This Pharmacopoeia contained both western and traditional system drugs commonly used in India. The same policy was continued while preparing the Indian Pharmacopoeia 1966. After eleven years, under the chairmanship of Dr. B. Mukherji the second edition of Indian Pharmacopoeia was released in 1966 with some modification. The supplement to the second edition of Indian Pharmacopoeia was published in 1975.

There had been a phenomenal growth and development of Indian pharma industry especially from early 1970 both in the range of active pharmaceutical ingredients (APIs) and the dosage forms produced. In view of these rapid advances, it was decided to publish a new edition of the Pharmacopoeia and its addenda at regular and shorter intervals for which the Indian Pharmacopoeia Committee was reconstituted in 1978. The third edition of the Indian Pharmacopoeia got published in 1985 under the chairmanship of Dr. Nityanand. Addendum/supplement I and II to third edition has been published in 1989 and 1991 respectively. In this Pharmacopoeia inclusion of traditional system of drugs was limited. However, most of the new drugs manufactured and/or marketed were included while only those herbal drugs which had definite quality control standards had got place in it.

In view of the continuing rapid increase in the range of drugs produced in India eleven year later the fourth edition of the Indian Pharmacopoeia was published under the chairmanship Dr. Nityanand in 1996. Addendum to fourth edition has been published initially in 2000 followed by in 2002 and 2005. In addition, supplement 2000 for veterinary products are also released. The addendum 2005 was published by the Indian Pharmacopoeia Committee which included a large number of antiretroviral drugs, and raw plants commonly used in making medicinal products not covered by any other Pharmacopoeias and attracted much global attention. The Indian Pharmacopoeia Committee decide to delete the obsolete or less used product monographs and added monographs based on the therapeutic merit, medicinal need and extent of use of such articles in the country.

The Indian Pharmacopoeia Commission (IPC) has been established in the year 2005. The IPC provided systematic approach and practices for publication of Indian Pharmacopoeia 2007 with focus on those drugs and formulations that cover the National health care programs and the national essential medicines. It contained monographs on antiretroviral, anticancer, anti- tubercular and herbal drugs. It further emphasized on biological monographs such as vaccines, immunosera for human use, blood products, biotechnological and veterinary (biological and non biological) preparations. Addendum 2008 to the Indian Pharmacopoeia 2007 was published which had taken care of the amendments to Indian Pharmacopoeia 2007 and also incorporated 72 new monographs.

The sixth edition of Indian Pharmacopoeia published in accordance with the principles and designed plan decided by the scientific body of the IPC. To establish transparency in setting standards for this edition, the contents of new monographs, revised appendices and other information have been published on the website of IPC, besides following conventional approach of obtaining comments. The feedback and inputs were reviewed by the relevant expert committee to ensure the feasibility and practicability of the standards and methods revised. The principle of openness, justice and fairness is kept in mind during compiling and editing the contents of this edition.

The IPC secretariat and Indian Pharmacopoeia laboratory staff, with the support of different advisory expert committee, and expert members of the scientific body have examined the suitability of the standards. In order to make Indian Pharmacopoeia 2010 user friendly, the existing formatting pattern has been suitably revised. The standards prescribed in this edition are encouraged to adhere with the concept of harmonization, keeping in view the technological status for manufacture and analysis of drugs and pharmaceuticals in the country without compromising with the quality of the products. It strives to update the existing monographs as well as incorporating the new monographs of drug substances based on clinical use of medicines in India and improving their test protocols.

The Indian Pharmacopoeia 2010 has been considerably revised and improved in respect of the requirements of monographs, appendices and testing protocols by introducing advanced technology. The contents of appendices are by and large revised in consonance with those adopted internationally. The monographs of special relevance disease of this region have been given special attention.

In addition emphasis has been put to bring out harmonization in appendices to establish a sound connection between individual monographs and the relevant appendices, so as to make this edition precise and well structured. Number of monographs and appendices are expanded further to incorporate the latest technological advancement and regulatory compliance. Constant efforts have been made to unify the national drug standards and to bring them in line with the international standards progressively, by addition of monographs of new drugs and adopting current methodology.

1.3.1 Features of various Editions of Indian Pharmacopoeia

1.3.2 Indian Pharmacopoeia 2010

This new edition of Indian Pharmacopoeia entitled sixth edition (Indian Pharmacopoeia 2010) was published by the IPC. It supersedes the fifth edition but any monograph of the earlier edition that does not figure in this edition continues to be official as stipulated in the second schedule of Drugs and cosmetics act, 1940.

Presentation

The Indian Pharmacopoeia 2010 comprises of three volumes. Each one volume has got different features. Volume I comprises notices, preface, about Indian Pharmacopoeia Commission, acknowledgements, introduction, general chapters and reference data. Volume II contains general notices, dosage forms (general monographs), drug substances, dosage forms and pharmaceutical aids (A to M). Volume III includes general notices, drug substances, dosage forms and pharmaceutical aids (N to Z), vaccines and immunosera for human use, herbs and herbal products, blood and blood related products, biotechnology products, veterinary products and index.

The scope of Pharmacopoeia has been extended to include products of biotechnology, indigenous herbs and herbal products, veterinary vaccines and additional antiretroviral drugs and formulations, inclusive of commonly used fixed dose combinations. Standards for new drugs and drugs used under national health programs are added and the drugs as well as their formulations not in use nowadays are omitted from this edition. The number of monographs of excipients, anticancer drugs, herbal products and antiretroviral drugs has been increased in this edition. Monographs of vaccines and immunosera are also upgraded in view of the development of latest technology in the field. A new chapter on liposomal products and a monograph of liposomal Amphotericin B injection is added advantage in view of latest technology adopted for drug delivery. A chapter on NMR is incorporated in appendices. The chapter on microbial contamination is also updated to a great extend to harmonize with prevailing international requirements.

1.3.3 Format

In an effort to make the Indian Pharmacopoeia more user’s friendly, design of the texts of the monographs and of the test methods are kept same like Indian Pharmacopoeia 2007. Cross referencing has been avoided to make each monograph complete in itself thus making it convenient to the analyst.

Basis of pharmaceutical requirements

As in the past, this compendium provides a publicly available statement concerning the quality of a product that can be expected and demonstrated at any time throughout the accepted shelf life of the article. The standards laid down represent the minimum with which the article must comply and it is inculcate on the manufactured in accordance with the GMPs. It is essential that sufficiently stringent limits are applied at the time of release of a batch of a drug substance or drug product so that the pharmacopoeial standards are met until its expiry date when stored under the storage conditions specified.

It must be noted that a valid interpretation of any requirement of Indian Pharmacopoeia should be done in the context of the monographs as a whole, the relevant general monograph, where appropriate, the specified tests and methods of analysis including any reference to relevant general notices. Familiarity with the general notices will facilitate the correct application of the requirements.

1.3.4 Changes

Keeping in view the essential requirement under the Drugs and Cosmetics Act, 1940 and rules there under in the information on category of a drug, dosage and usual available strengths of dosage forms have been kept in this edition.

General chemical tests for identification of an article have been almost eliminated and the more specific infrared and ultraviolet spectrophotometric tests have been given emphasis. The concept of relying on published infrared spectra as a basis for identification has been continued.

The use of chromatographic methods has been greatly extended to cope with the need for more specificity in assays and in particular, in assessing the nature and extend of impurities in drug substances and drug products. Most of the existing assays and related substances tests are upgraded by liquid chromatography method in view to have more specificity and to harmonize with other international Pharmacopoeias.

The test for pyrogens involving the use of animals has been virtually eliminated. The test for bacterial endotoxins introduced in the previous edition is now applicable to more items. The test for abnormal toxicity is now confined to certain vaccines.

1.3.5 General Chapters

Volume I is devoted mainly to test methods that are applicable to all the articles of the Indian Pharmacopoeia and general information pertaining to the quality requirements of medical substances. It also includes reference data such as reference spectra, typical chromatograms etc. The test methods reflect the sophistication of analytical methodology and instrumentation.

Analytical methods are, in general, in harmony with those adopted internationally for monitoring the quality of drugs. The steps taken for harmonization have been initiated by the need to cope with the increasing demand for drugs manufactured in the country to meet globally accepted standards.

The trend towards controlling the microbial quality of all medicinal products have been recognized and the requirement regarding limits of bacterial contamination even of products for oral administration and topical application so that adequate controls are exercised by manufactures by the adoption of Good Manufacturing Practices (GMPs) has been continued.

The chapter on vaccines: General requirements has been updated. Minor corrections have been made in the appendices entitled tests on chicken flocks free from specified pathogens for the production and quality control of vaccines and general provisions. Avian viral vaccines – tests for extraneous agents in seed lot. The peptide mapping test for inactivated Hepatitis B vaccine has been deleted. Wherever appropriate, other corrections has also been incorporated and over all presentation improved.

In view of considering the microbiological quality, the whole microbiological general chapter comprising of effectiveness of antimicrobial preservatives, microbial contamination in non sterile products and microbiological quality of raw material, dosage forms, herbs, processed herbs and herbal products have been extensively revised. For the first time in this chapter the analysis of certain Shigella boydii (strain of tropical region of our country) is made essential as it causes acute dysentery.

The chapter on biotechnology derived therapeutic products has been fully revised. Special emphasis given on monoclonal antibodies and antisera.

The standards prescribed in the Indian Pharmacopoeia are to establish the compliance with regulatory requirements on article. The criteria to be adhered are; a) The interpretation of a monograph must be in accordance with all the general requirements, testing methods, texts and notices pertaining to it, in the Indian Pharmacopoeia. b) A product is not of standard quality unless it complies with all the requirements of the monograph.

This edition of Indian Pharmacopoeia 2010 supersedes the Indian Pharmacopoeia 2007 edition. The Indian Pharmacopoeia 2010 incorporated 287 new monographs consisting of APIs, excipients, dosage forms and herbal products, etc. This Indian Pharmacopoeia edition plays a significant role in improving the quality of medicines which in turn promote public health and accelerate the growth and development of pharma sector.

In Pharmacopoeia under a monograph each pharmaceutical agent has been described. In appendices of the Pharmacopoeia the various standards for chemical apparatus, technique processes etc. are described. Appendices are considered as important as the main body monographs for a pharmaceutical chemist and an analyst. In the Pharmacopoeia those pharmaceuticals which are commonly used in the recent past have been included. Substances which have proved to be undesirable from past experience are removed from Pharmacopoeia. In general due to idleness, substances which are commercially available in excellent purity and are commonly used for other purposes are also not included. In case, if such substances find use internally then they are included in the monographs. The standards prescribed for a chemical are the minimum. It does not prevent a manufacturer from supplying these with more stringent standards. In the Pharmacopoeia if a substance has not been included it does not imply that it cannot be used or marketed. Such non official substances must correspond to standards prescribed either in the earlier editions of the Indian Pharmacopoeia or in other recognized pharmacopoeia (of other countries).

Generally in India products corresponding to the British Pharmacopoeia (BP) and United States Pharmacopoeia (USP) are marketed. Other better known Pharmacopoeias are International Pharmacopoeia (IP), European Pharmacopoeia (EP) and Union of Soviet Socialist Republics Pharmacopoeia (USSRP). To avoid confusion with International Pharmacopoeia, Indian Pharmacopoeia sometimes abbreviated as IND.P. or PI Generally IP will be understood as Indian Pharmacopoeia unless otherwise specified in our country. The various other compendia prescribing standards for pharmaceuticals are British Pharmaceutical Codex (BPC) and National Formulary (NF). In the interest of proper health any substance which fails to correspond to any official standard should not be used.

Official substances: In the latest edition of the Pharmacopoeia those drugs and pharmaceuticals are termed as official substances in that country of Pharmacopoeia. It is very important to understand the difference between an official substance and chemical individual with same name. The individual chemical can be pure to any specified purity. The official substance is a commercial product which is required to comply with standards specified in the Pharmacopoeia and may often have some other substances added for specific reasons. For example, to prevent the formation and to inactivate any poisonous phosgene (carbonyl chloride) gas that may be formed in contact with the air during storage of chloroform of the Pharmacopoeia contains 1-2 % of added ethyl alcohol.

1.3.6 Pharmacopoeial Description/Presentation

Most of the Pharmacopoeias including Indian Pharmacopoeia consist of the three major sections namely

(a)   Introduction including general notices

(b)   Monographs of the official drugs

(c)   Appendices.

(a)   Introduction: It is a useful pointer to pharmaceutical progress since last edition. It summarizes the different changes including additions/deletions in the current edition compared to last edition. To avoid misinterpretation and misunderstanding of later parts of the text, attention should be paid to general notices at the outset.

(b)   Monographs: The general monographs for dosage forms of active pharmaceutical ingredients (APIs) are grouped together at the beginning of volume II of Indian Pharmacopeia 2010. They are followed by the monographs for the APIs, pharmaceutical aids and individual dosage forms all in alphabetical order. Monographs for other articles of a special nature such as vaccines and immunosera for human use, herbs and herbal products, blood and blood related products, biotechnology products, veterinary products are given in separate sections in volume III of Indian Pharmacopeia 2010.

The written study of a subject was implied by the word monograph. These are considered as very important because medicinal substances are used for the cure and/or prevention of diseases. Therefore their written studies appear as monographs in the Pharmacopoeia. These monographs are arranged in the alphabetical order of their names and are somewhat stereotyped in style. The following information about the drugs and pharmaceutical aids are described in Pharmacopoeial monographs.

1.3.7 General Monographs

General monographs on dosage forms include requirements of general application and apply to all preparations within the scope of the introduction section of the general monograph, except where a preamble limits the application. The requirements are not necessarily comprehensive for a given specific preparation, additional requirements may sometimes be given in the individual monograph for it.

1.3.8 Production

Statements given under the heading production relate to particular aspects of the manufacturing process and are not necessarily comprehensive. However, they are mandatory instructions to manufacturers. For example, they may relate to source materials, to the manufacturing process and its validation and control, to any process testing that is to be carried out by the manufacturer on the final product either on selected batches or on each batch prior to release. All this cannot be verified on a sample of the final product by an independent analyst. It is for the licensing authority to verify that the instructions have been followed.

The absence of a section on production does not imply that attention to features such as those given above is not required. An article described in a monograph of the Pharmacopeia is to be manufactured in accordance with the principles of good manufacturing practice and in accordance with the requirements of the Drugs and Cosmetic Rules, 1945. The general principles applicable to the manufacture and quality assurance of drugs and preparations meant for human use equally to veterinary products as well.

1.3.9 Manufacture of Drug Products

The opening definitive statement in certain monographs for drug product is given in terms of the active ingredient(s) only. Any ingredient(s) other than those included in the statement, must comply with the general notice on excipients and the product must conform to the Pharmacopoeial requirements.

Official preparations are prepared only from ingredients that comply with the requirements of the Pharmacopoeial monographs for those individual ingredients for which monographs are provided.

1.3.10 Excipients

Any substance added in preparing an official preparation shall be innocuous, shall have no adverse influence in the therapeutic efficacy of the active ingredients and shall not interfere with the tests and assays of Pharmacopoeia. Care should be taken to ensure that such substances are free from harmful organisms.

1.3.11 Individual Monographs

Drug products that are the subject of an individual monograph are also required to comply with the tests given in the general monographs.

1.   Title: The main title for a drug substance is the International Non-proprietary Name (INN) approved by World Health Organization (WHO). The official name of the compound in English is stated in the title. In place of the main title, sometimes sub titles are given which are synonyms/subsidiary names; where included, they have the same significance as the main title. For example, calcium carbonate can also be called precipitated chalk; iron and ammonium citrate can also be called ferric ammonium citrate and milk of magnesia can also be called magnesium hydroxide mixture.

When a product contains one or the other different salts of an active molecule, the main title is based on the full name of the active ingredient. For example, chloroquine phosphate tablet and chloroquine sulphate tablets.

2.   Chemical formulae: When the chemical structure of an official substance is known or generally accepted, the graphic and molecular formulae are normally given at the beginning of the monograph for information. To specify the absolute stereo chemical configuration International Union of Pure and Applied Chemists (IUPAC) systems have been used. If the substance is enantiomer, the sign of optical rotation has been attached to the systematic name.

3.   Atomic and molecular weight: The atomic and molecular weight is shown, as and when appropriate at the top right hand corner of the monograph. For example, magnesium chloride (Molecular weight: 202.30) and potassium permanganate (Molecular weight: 158.03). In general if the correct chemistry is not known or the compound is of indefinite composition these two items are not provided. For example chemical formula and molecular weight for iron ammonium citrate are not provided.

4.   Definition: The opening statement of a monograph is one that constitutes an official definition of the substance, preparation or other article that is the subject of the monograph. In some monographs of pharmaceutical preparations the statement is given in terms of principle ingredient(s). In monographs on vegetable drugs, the definition indicates whether the subject of the monograph is, for example, the whole drug or the drug in powdered form. Certain pharmaceutical substance and other articles are defined by reference to a particular method of manufacture.

5.   Statement of content: The limits of content stated are those determined by the method described under assay.

6.   Category: This part of monograph expresses the pharmacological or therapeutic or pharmaceutical application of the compound. Although the compound may have other applications usually this part describes the main application. Analgesics, antibiotic, antacid, laxative etc. are some of the main categories for inorganic pharmaceuticals in the Pharmacopoeia.

7.   Dose: Dose mentioned in the Pharmacopeia is intended merely for general guidance and represent, unless otherwise stated, the average range of quantities which are generally regarded as suitable for adults when administered by mouth. It provides the quantity guidance to the prescriber or the physician to achieve the desired therapeutic effects in adults. The dose can be altered as and when required. For example the dose of calcium carbonate is 1 – 5 gm.

This is omitted for substances not used for internal administration. Usual strength may be given for pharmaceutical dosage forms like injection etc. which is the most commonly marketed dosage strength.

8.   Usual strength: It indicates the strength(s) usually marketed for information of the pharmacist and the medical practitioner.

9.   Description: This part of monograph is not to be interpreted in a strict sense and is not to be regarded as official requirements. It illustrates a physical description of the substance such as amorphous nature or crystalline, odor, color and taste etc. In the preliminary evaluation of the integrity of an article these properties help and not themselves the standards or tests or purity. For example, Calcium carbonate is a fine white microcrystalline powder, odorless and tasteless.

10.   Solubility: The solubility mentioned in Indian Pharmacopeia is the approximate solubility at a temperature between 15 °C and 30 °C, unless otherwise stated, and are not to be considered as official requirements. In the Pharmacopoeia under general notices solubility is described. The solubility of a substance in water, hot or boiling water, alcohol, glycerol, other organic solvent, acid and alkali were given.

11.   Test methods: References to general methods of testing are indicated by test method numbers in brackets immediately after the heading of the test or at the end of the text.

12.   Identification: These identification tests are not a proof of identity. This usually involves specific chemical test or tests for identifying the substance. It provides a means of verifying that the identity of the material under examination is in accordance with the label on the container. In certain monographs alternative series of tests are given; compliance with either one or the other set of tests is adequate to verify the identity of the article. In general for inorganic pharmaceuticals color reactions, precipitation reactions and gas evolving reactions are used. For example, Phenol gives violet color with ferric chloride.

13.   Tests and assay: These are the official methods upon which the standards of Pharmacopoeia depend. The requirements are not framed to take into account all possible impurities. Tests and assay are prescribed for the minimum sample available on which the attributes of the article should be measured. Assurance of quality must be ensured by the manufacture by the use of statistically valid sampling and testing programs.

14.   Tests: In general the assays and test are carried out at a temperature between 20 °C and 30 °C unless otherwise stated. Precaution should be taken to avoid exposure to direct sunlight or other strong light where it is directed that an analytical operation is to be carried out in subdued light. Similarly precaution should be taken to exclude actinic light by the use of low actinic glassware, working in a dark room or similar procedures where a procedure is directed to be performed protected from light. For preparations other than those of fixed strength, the quantity to be taken for a test or an assay is usually expressed in terms of the active ingredient. It means that the quantity of the active ingredient expected to be present and the quantity of the preparation to be taken are calculated from the strength stated on the label.

15.   Other tests: In the monographs on dosage forms and certain preparations, under the sub heading other tests it is stated that an article complies with the tests stated under the general monograph of the relevant dosage form or preparation. Details of such tests are illustrated in the general monographs.

16.   Limits: The limits given are based on data obtained in normal analytical practice. They take into account normal analytical errors, of acceptable variations in manufacture and of deterioration to an extent that is acceptable. No further tolerances are to be applied to the limits for determining whether or not the article under examination complies with the requirements of the monograph.

17.   Quantities: Unless otherwise stated, in tests with numerical limits and assays, the quantity stated to be taken for testing is approximate. Volumes stated in microliters (µl) are measured using a micropipette or micro syringe. The term transfer is used generally to indicate a quantitative operation.

18.   Apparatus: Measuring and weighing devices and other apparatus are described in the chapter entitled apparatus for tests and assays. Unless otherwise stated, comparative tests are carried out using identical Nessler cylinders.

19.   Reagents and solutions: The reagents required for the tests and assays of the drugs in the Pharmacopoeia are defined in the various chapters showing their nature, degree of purity and the strengths of the solutions to be made from them.

20.   Indicators: Where the use of an indicator solution is mentioned in an assay or test, approximately 0.1 ml of the solution shall be added, unless otherwise directed.

21.   Reference substances: These are the authentic specimens chosen and verified on the basis of their suitability for intended use as prescribed in the Pharmacopoeia and not necessarily suitable in other circumstances.

22.   Test animals: Unless otherwise directed, animals used in test or assay shall be healthy and are drawn from a uniform stock, and have not been previously treated with any material that will interfere with the test or the assay.

23.   Calculation of results: The results should be calculated to one decimal place more than the significant figures stated and then rounded up or down as follows; if the last figure calculated is 5 – 9, the preceding figure is increased by 1; if it is 4 or less, the preceding figure is left unchanged.

24.   Storage: These directions are useful in preserving the activity of the chemical. Specific directions are given in some monographs with respect to the temperatures at which Pharmacopoeial article should be stored, where it is considered that usage at a lower or higher temperature may produce undesirable results. The storage conditions are defined by the following terms; a) Store in a dry, well ventilated place at a temperature not exceeding 30 °C, b) Store in a refrigerator (2 °C to 8 °C) and do not freeze, c) store in a freezer and d) Store in a deep freezer (below -18 °C). The storage conditions not related to temperature are indicated in the following terms; a) Store protected from light and b) Store protected from light and moisture. Where no specific storage directions or limitations mentioned, it is to be understood that the storage conditions include protection from moisture, freezing and excessive heat (any temperature above 40 °C). For example insulin injection store in multiple dose containers at a temperature between 2 °C to 8 °C. It should not be allowed to freeze.

25.   Storage containers: The storage containers in the Pharmacopoeia are indicated in the following terms; a) Well closed containers: This implies the substance is stable and gets protected from dust, dirt, insects etc, getting into the container, b) Tightly closed container: The substances in such cases get affected by atmospheric oxygen or moisture or carbon dioxide. For example, reducing agents, hygroscopic substances, strong bases etc. must be stored in tightly closed containers. It may also include such compounds are volatile or contain dissolved gases etc. c) Light resistant container: Substances which are affected by light are stored in amber or dark colored containers, d) Single dose containers: This is generally prescribed for some injectables which once opened should not be used again. For example, Ferrous fumarate (Store in a light resistant container).

26.   Labeling: The labeling of drugs and pharmaceuticals is governed by the Drugs and Cosmetics Rule, 1945. The statements that are given in the monographs under the side heading labeling are not comprehensive. Only those that are necessary to demonstrate compliance or otherwise with the monograph have been given and they are mandatory. For example, in the monograph on betamethasone sodium tablets the labeling statement is The label states the strength in terms of the equivalent amount of betamethasone. Any other statements may also include as recommendations.

(c)   Appendices: A comprehensive section of appendices are presented followed by the general notices and monographs. The apparatus that are needed for various Pharmacopoeial tests and assays are described in the appendix 1. Biological tests and assays are described in appendix 2. The details of various chemical tests and assays are included in appendix 3. The details of microbiological tests and assays are included in appendix 4. In the appendix 5, some physical tests and determinations like loss on drying, determination of pH, melting range etc are described. Appendix 6 includes the useful directions on cleaning glassware. Appendix 7 describes the reagents and solutions needed for the various tests and assays, their method of preparation, standards etc. Appendix 8 describes reference substances. Appendix 9 have been described fully the names, symbols used in the Pharmacopoeia for weights and measures and of elements and their atomic weights have been described.

1.3.12 Representative example of a Monograph of Indian Pharmacopoeia 2010

Ferrous Gluconate

Mol. Formula C12H22FeO14.xH2O      Mol. Wt: 446.1 (anhydrous)

Ferrous Gluconate is ferrous di (D-gluconate).

Ferrous Gluconate contains not less than 95.0 percent and not more than 102.0 percent of C12H22FeO14, calculated on the dried basis.

Category : Haematinic.

Dose: Prophylactic, 600 mg daily; therapeutic, 1.2 to 1.8 g daily, in divided doses.

(300 mg of ferrous gluconate is approximately equivalent to 35 mg of ferrous iron).

Description: A yellowish grey or pale greenish–yellow, fine powder or granules, odour, slight, resembling that of burnt sugar.

Identification

(a)   Dissolve 5 gm in carbon dioxide –free water at 60 °C, cool and dilute to 50 ml with water. 1 ml of the resulting solution gives reaction A of ferrous salts.

(b)   Determine by thin layer chromatography, coating the plate with silica gel G.

Mobile phase.A mixture of 10 volumes of concentrated ammonia, 10 volumes of ethyl acetate, 30 volumes of water and 50

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